Amyloid-beta fibrillar plaque (Aβ)

Amyloid-beta (Aβ) fibrillar plaques are extracellular accumulations of misfolded Aβ peptides, primarily Aβ42, which are hallmark pathological features of Alzheimer's disease (NIH, 2023). These plaques form through the proteolytic cleavage of the amyloid precursor protein (APP) by beta- and gamma-secretases, leading to the self-assembly of monomers into oligomers, protofibrils, and eventually insoluble fibrillar structures (Jack et al., 2018). While the amyloid hypothesis suggests that these plaques are central to neurodegeneration, recent therapeutic strategies focus on clearing existing plaques or preventing their formation to slow cognitive decline. Drugs targeting these plaques, such as monoclonal antibodies, aim to reduce the amyloid burden in the brain by stimulating immune-mediated clearance via microglial activation (FDA, 2023). However, the removal of vascular amyloid can lead to safety concerns like Amyloid-Related Imaging Abnormalities (ARIA), characterized by edema or hemorrhage (Sperling et al., 2011). Despite controversies regarding the correlation between plaque removal and clinical benefit, several anti-amyloid therapies have recently received regulatory approval for early-stage Alzheimer's disease.

Other names

Amyloid-beta plaquesSenile plaquesNeuritic plaquesAβ plaquesAmyloid-beta peptide aggregatesBeta-amyloid plaques

Monoclonal antibodies bind to specific epitopes on amyloid-beta fibrils or plaques, facilitating their clearance by microglia through Fc-mediated phagocytosis or preventing further aggregation of soluble species into insoluble fibrils (Cummings et al., 2022; FDA, 2023).